Clinical impact of fungal colonization of burn wounds in patients hospitalized in the intensive care unit: a retrospective cohort study.

Background: Invasive fungal infections in burn victims significantly increase mortality and hospitalization. The effect of fungal burn wound colonization has not been established. Methods: All adult patients hospitalized in the intensive care unit (ICU) with burns ≥10% of total body surface area (TBSA) between 2005 and 2021 were included. Superficial swabs were collected whenever clinical suspicion of wound colonization was raised, and deep tissue samples were sent at any wound excision. The primary outcome was the incidence of invasive fungal infections defined as any deep tissue fungal infection or fungemia. Results: Of 242 patients included, 39 (16.1%) had fungal wound colonization, 22 (56.4%) with yeasts and 24 (61.5%) molds. Patients with fungal colonization had a significantly higher rate of invasive fungal infections (82.1% vs 3.9%, p<0.001), candidemia (15.4% vs 3.4%, p=0.002), as well as longer ICU stay (61.5±57.6 vs 19±40.5 days, p<0.001), and higher in-ICU mortality (43.6% vs 15.8%, p<0.001). Survival analysis showed fungal colonization to be associated with significantly increased risk of invasive infection (aHR 25, 95% CI (9.67 to 64.62)), even when adjusted for age, TBSA, sequential organ failure assessment scores, Charlson Comorbidity Index and the presence of bacteremia. Conclusions: Fungal burn wound colonization is associated with increased risk of invasive fungal infections and mortality. Level of Evidence: This a single center, retrospective cohort study.

A deep look into the storm: Israeli multi-center experience of coronavirus disease 2019 (COVID-19) in patients with autoimmune inflammatory rheumatic diseases before and after vaccinations.

Objective: We aimed to characterize the course of COVID-19 in autoimmune inflammatory rheumatic disease (AIIRD) patients in Israel, taking into consideration several remarkable aspects, including the outcomes of the different outbreaks, the effect of vaccination campaigns, and AIIRD activity post-recovery. Methods: We established a national registry of AIIRD patients diagnosed with COVID-19, including demographic data, AIIRD diagnosis, duration and systemic involvement, comorbidities, date of COVID-19 diagnosis, clinical course, and dates of vaccinations. COVID-19 was diagnosed by a positive SARS-CoV-2 polymerase chain reaction. Results: Israel experienced 4 outbreaks of COVID-19 until 30.11.2021. The first three outbreaks (1.3.2020 - 30.4.2021) comprised 298 AIIRD patients. 64.9% had a mild disease and 24.2% had a severe course; 161 (53.3%) patients were hospitalized, 27 (8.9%) died. The 4th outbreak (delta variant), starting 6 months after the beginning of the vaccination campaign comprised 110 patients. Despite similar demographic and clinical characteristics, a smaller proportion of AIIRD patients had negative outcomes as compared to the first 3 outbreaks, with regards to severity (16 patients,14.5%), hospitalization (29 patients, 26.4%) and death (7 patients, 6.4%). COVID-19 did not seem to influence the AIIRD activity 1-3 months post-recovery. Conclusions: COVID-19 is more severe and has an increased mortality in active AIIRD patients with systemic involvement, older age and comorbidities. Vaccination with 3 doses of the mRNA vaccine against SARS-CoV-2 protected from severe COVID-19, hospitalization and death during the 4th outbreak. The pattern of spread of COVID-19 in AIIRD patients was similar to the general population.

Switching from intravenous tocilizumab to subcutaneous administration during COVID-19 pandemic: impact on treatment efficacy and patient satisfaction.

OBJECTIVES: We aimed to assess the efficacy and patient satisfaction of subcutaneous tocilizumab (SC TCZ) in patients previously treated with intravenous tocilizumab (IV TCZ) during the COVID-19 pandemic. METHODS: We conducted a single-centre retrospective study at the Rheumatology Day Care at the Rheumatology Institute, Rambam Health Care Campus, Israel. Clinical and laboratory data of IV TCZ treated patients who switched to SC TCZ were retracted and analysed. Data were collected from the last two visits before switching to SC treatment and two visits afterwards. A telephone call conversation was conducted for all patients who continued SC treatment and did not come to follow-up visits. RESULTS: Forty patients (age 53.03 (± 15.7)) treated with IV TCZ were switched to SC TCZ in April-May 2020. Three patients were excluded from the study. Most of the patients were treated with TCZ for 6.35 (±2.89) years and had low disease activity. 26/37 (70%) patients discontinued SC TCZ therapy and switched back to IV TCZ. The majority of discontinuations were due to flare up of the underlying disease reflected by increased number of tender and/or swollen joints, prolongation of morning stiffness or increased pain VAS score. Two patients were hospitalised for IV glucocorticoids and 1 patient underwent knee arthrocentesis. 11/37 (30%) patients continued SC TCZ treatment. 3/11 (27%) expressed less satisfaction with SC TCZ therapy. CONCLUSIONS: More than half of the patients who switched from IV TCZ to SC TCZ showed signs of flare of their underlying disease or were less satisfied with SC treatment.

[THE INPUT OF MEASURING INFLIXIMAB LEVELS AND LEVELS OF ANTIBODIES TO INFLIXIMAB IN THE MANAGEMENT OF PATIENTS WITH RHEUMATIC DISEASES].

BACKGROUND: High levels of infliximab (IFX) directed antibodies (IFX-Ab) may result in significant reduction in IFX concentration and loss of drug efficacy. OBJECTIVES: To assess the input of measuring serum IFX levels and levels of IFX-Ab in the management of rheumatic diseases. METHODS: Serum levels of IFX and anti-IFX-Ab were measured by ELISA (IFX-Abs were also identified by anti-human lambda chain Ab) and correlated to patients (responders and nonresponders) disease activity scores. RESULTS: A total of 144 tests for IFX were performed in 91 patients (mean age 50.2 years and disease duration 9.9 years). Among responders (57 patients) levels (mean, median) of IFX were significantly higher than in non-responders (34 patients) (4.2 mcg/ml (2.3) versus 1.1 mcg/ml (0.45)); levels of IFX-Ab in responders were significantly lower than in non-responders (4.59 mcg/ml (1.0) versus 13.1 (6.1)). High IFX-Ab levels predicted IFX discontinuation in 8.8% of responders and 55.9% among non-responders. In non-responders with low IFX levels and low IFX-Ab, the shortening of re-treatment intervals lead to significant improvement. In about 28% of patients, results of blood tests influenced treatment decisions. CONCLUSIONS: Assessment of immunogenicity of anti-TNF monoclonal antibodies proved useful information for guiding the therapy in rheumatic diseases with suboptimal clinical response. Patients with low IFX levels and low levels of IFXAb may benefit from increasing the drug dose or decreasing of re-treatment intervals. In patients with negligible serum levels of IFX and high levels of IFX-Ab, the therapy should be switched to another biological agent, probably with a different mechanism of action.

Rituximab: rescue therapy in life-threatening complications or refractory autoimmune diseases: a single center experience.

Rituximab (RTX) is a chimeric anti-CD20 antibody, approved for rheumatoid arthritis (RA) patients who failed anti-Tumor Necrosis Factor therapy. It has been used occasionally for life-threatening autoimmune diseases (AID). We report our center experience in the use of RTX in life-threatening complications or refractory AID. Clinical charts of patients treated with RTX at our center were reviewed, cases treated for life-threatening complications or refractory AID were analyzed. Acute damage to vital organs such as lung, heart, kidney, nervous system with severe functional impairment were defined as life-threatening complications; treatment failure with high-dose corticosteroids, cyclophosphamide, IVIG, plasmapheresis was defined as refractory autoimmune disease. During the years 2003-2009, 117 patients were treated with RTX, most of them for RA. Nine patients (6 females, mean age 51.5 years, mean disease duration 6.3 years) answered the criteria. The indications were as follows: pulmonary hemorrhage (1 patient with cryoglobulinemic vasculitis, 1 with systemic sclerosis, 1 with ANCA-associated vasculitis), catastrophic anti-phospholipid syndrome (2 SLE patients), non-bacterial endocarditis and pulmonary hypertension (1 patient with mixed connective tissue disease), vasculitis and feet necrosis (1 patient with systemic lupus erythematosus), severe lupus demyelinative neuropathy and acute renal failure (1 patient), and severe rheumatoid lung disease with recurrent empyema and pneumothorax (1 patient). B cell depletion was achieved in all patients. The median time since starting of complications to RTX administration was 3 weeks (range 2-15 weeks). Complete remission (suppression of the hazardous situation and return to previous stable state) was seen in 7 out of 9 patients. Partial remission (significant improvement) was achieved in the remained. The median time to response was 3 weeks (range 1-8 weeks), mean follow-up 47.2 months (range 6-60 months). A rapid tapering off of steroids was achieved in all patients. Two patients relapsed and were successfully retreated with RTX: the patient with severe RA lung relapsed after 3 years, one of the patients with ANCA-associated pulmonary alveolar hemorrhage relapsed after 10 months. There were no side effects during RTX infusion. Two episodes of serious infections were registered: fatal Gram-negative sepsis 6 months after RTX treatment, and septic discitis 4 months after receiving RTX. RTX serves as a safe, efficient, and prompt rescue therapy in certain life-threatening conditions and resistant to aggressive immunosuppression AID. RTX when administrated at an earlier stage, prevented irreversible vital organ damage, and allowed rapid steroid tapering off in already severe immunodepressed patients.

Anti-tumor necrosis factor therapy: 6 year experience of a single center in northern Israel and possible impact of health policy on results.

BACKGROUND: Infliximab and etanercept have been included in the Israeli national list of health services since 2002 for rheumatoid arthritis and juvenile idiopathic arthritis, and since 2005 for psoriatic arthritis and ankylosing spondylitis. The regulator (Ministry of Health and health funds) mandates using fixed doses of infliximab as the first drug of choice and prohibits increased dosage. For other indications (e.g., vasculitis), anti-tumor necrosis factor therapy is given on a "compassionate" basis in severe refractory disease. OBJECTIVES: To describe our experience with anti-TNF therapy in a single tertiary referral center in northern Israel and to analyze the impact of the national health policy on the results. METHODS: We reviewed the medical records of patients who received anti-TNF therapy in our institution, and analyzed demographic data, diagnosis, clinical and laboratory features, previous and current therapies, and anti-TNF treatment duration and side effects. RESULTS: Between 2001 and 2006, 200 patients received anti-TNF therapy for rheumatoid arthritis (n = 108), juvenile idiopathic arthritis (n = 11), psoriatic arthritis (n = 37), ankylosing spondylitis (n = 29), adult Still's disease (n = 4), overlap disease (RA and scleroderma or polymyositis, n = 6), temporal arteritis (n = 1), polyarteritis nodosa (n = 1), dermatomyositis (n = 1), amyloidosis secondary to RA (n = 1) and Wegener's granulomatosis (n = 1). Forty percent of RA patients discontinued the first anti-TNF agent due to side effects or insufficient response. Higher sedimentation rate and lower or negative rheumatoid factor predicted better response to therapy among RA patients. AS and PS patients had a better safety and efficacy profile. Severe infections occurred in 2% of patients. All eight patients who presented lung involvement as part of their primary rheumatic disease remained stable or improved. A significant improvement was achieved in all six patients with overlap disease. CONCLUSION: Our daily practice data are generally in agreement with worldwide experience. The 'deviations' might be explained by the local health policy at that time. The impact of health policy and economic and administrative constraints should be taken into account when analyzing cohort daily practice data.